Trypanosome variant surface glycoprotein transfer to target membranes: a model for the pathogenesis of trypanosomiasis.
The variant surface glycoprotein (VSG) of trypanosomes is attached to the cell surface by means of a phosphatidylinositol-containing glycolipid membrane anchor. The studies presented in this paper support the hypothesis that the transfer of VSG from trypanosomes to erythrocytes could lead to one of the pathological features associated with trypanosome infection--i.e., anemia. Migration of trypanosome VSG from live trypanosomes to target cells (sheep erythrocytes) could be shown by preincubating erythrocytes with trypanosomes and subsequently testing the washed erythrocytes for insertion of VSG by their susceptibility to lysis by complement in the presence of an anti-VSG antibody. Complement-mediated lysis was found to depend on the strain-specific anti-VSG antibody used. Extent of erythrocyte lysis increased with time of cell exposure to trypanosomes and with trypanosome concentration. No erythrocyte lysis was observed when trypanosomes were preincubated with anti-VSG antibody before adding erythrocytes. Purified membrane-form VSG (which retains the glycolipid anchor), but not soluble VSG (which no longer has the terminal diacylglycerol moiety), could sensitize erythrocytes to anti-VSG antibody-mediated complement lysis. The intermembrane transfer of VSG from trypanosomes to cells of the infected host could provide a molecular mechanism for the pathogenesis of trypanosomiasis.
Rifkin
M R
MR
Rockefeller University, New York, NY 10021.
Landsberger
F R
FR
D000818:Animals; D003165:Complement System Proteins / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology*; D006461:Hemolysis; D006801:Humans; D008954:Models, Biological; D009439:Neuraminidase / Q000494:pharmacology; D012756:Sheep; D014346:Trypanosoma brucei brucei / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000469:parasitology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000502:physiology*
D014643:Variant Surface Glycoproteins, Trypanosoma; D003165:Complement System Proteins; D009439:Neuraminidase